COVID-19, SARS-CoV-2
Conditions
Keywords
COVID-19 Vaccine
Brief summary
The aim of the study is to assess the safety, efficacy, and immunogenicity of AZD1222 for the prevention of COVID-19.
Detailed description
The COVID-19 pandemic has caused major disruption to healthcare systems with significant socioeconomic impacts. Currently, there are no specific treatments available against COVID-19 and accelerated vaccine development is urgently needed. A safe and effective vaccine for COVID-19 prevention would have significant public health impact.
Interventions
BIOLOGICALAZD1222
AZD1222 is a recombinant replication-defective chimpanzee adenovirus expressing the SARS-CoV-2-5 surface glycoprotein.
BIOLOGICALPlacebo
Commercially available 0.9% (n/V) saline for injection.
Sponsors
Iqvia Pty Ltd
AstraZeneca
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
QUADRUPLE (Subject, Caregiver, Investigator, Outcomes Assessor)
Masking description
Double Blind: two or more parties are unaware of the intervention assignment.
Intervention model description
Participants are assigned to one of two or more groups in parallel for the duration of the study.
Eligibility
Sex/Gender
ALL
Age
18 Years to 130 Years
Healthy volunteers
Yes
Inclusion criteria
* Increased risk of SARS-CoV-2 infection * Medically stable
Exclusion criteria
* confirmed or suspected immunosuppressive or immunodeficient state * significant disease, disorder, or finding * Prior or concomitant vaccine therapy for COVID-19
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Number of Participants With Binary Response | From 15 days post second dose up to data cut-off date (DCO) of 05 March 2021 or study discontinuation or unblinding or receipt of non-study COVID-19 vaccination, up to a maximum of 17 weeks | A binary response, whereby a participant with negative serostatus at baseline is defined as a COVID-19 case if their first case of SARS-CoV-2 RT-PCR-positive symptomatic illness occurs ≥ 15 days post second dose of study intervention. Otherwise, a participant is not defined as a COVID-19 case. The primary efficacy analysis was performed once approximately 150 events meeting the primary efficacy outcome measure definition had occurred across the AZD1222 and placebo groups. |
| Number of Participants With Adverse Events (AEs) Post Each Dose of Study Intervention | From Day 1 up to 28 days post second dose of study intervention, approximately 57 days | An AE is the development of any untoward medical occurrence in a clinical study participant administered medicinal product and which does not necessarily have a causal relationship with this medicinal product. An AE can therefore be any unfavorable and unintended sign, symptom, or disease temporally associated with the use of a medicinal product, whether or not considered related to the medicinal product. |
| Number of Participants With Serious Adverse Events (SAE), Medically Attended Adverse Events (MAAE), and Adverse Event of Special Interest (AESI) Prior to Non-study COVID-19 Vaccination | From Day 1 up to receipt of non-study COVID-19 vaccination or a maximum of Day 760 for participants without non-study COVID-19 vaccination. | An SAE is an AE occurring during any study phase that fulfils 1 or more of the following criteria: death; immediately life-threatening; in-participant hospitalization or prolongation of existing hospitalization; persistent or significant disability or incapacity; congenital abnormality or birth defect; an important medical event. AESIs were events of scientific and medical interest specific to the further understanding of the study intervention safety profile and required close monitoring and rapid communication by the investigators to the sponsor. MAAEs are defined as AEs leading to medically-attended visits that were not routine visits for physical examination or vaccination, such as an emergency room visit, or an otherwise unscheduled visit to or from medical personnel (medical doctor) for any reason. Different follow-up time between AZD1222 and Placebo groups (20223 versus 3893 participant years). |
| Number of Participants With Local and Systemic Solicited AEs in the Substudy Only | From Day 1 up to 7 days post each dose of study intervention, approximately 14 days | Solicited AEs are local or systemic predefined events for assessment of reactogenicity. Solicited AEs were collected in a e-Diary only for participants in the substudy. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Number of Participants With COVID-19 Severe or Critical Symptomatic Illness Post Second Dose of Study Intervention | From 15 days post second dose up to DCO of 05 March 2021 or study discontinuation or unblinding or receipt of non-study COVID-19 vaccination, up to a maximum of 17 weeks | The incidence of SARS-CoV-2 RT-PCR-positive severe or critical symptomatic illness occurring ≥ 15 days post second dose of study intervention. The severity of COVID-19 was evaluated in participants with symptoms of COVID-19. Following are the findings regarding severe of critical symptomatic COVID-19: clinical signs at rest indicative of severe systemic illness; respiratory failure; evidence of shock; significant acute renal, hepatic, or neurologic dysfunction; admission to an intensive care unit; and death (key secondary endpoint). |
| Number of Participants With COVID-19 Severe or Critical Symptomatic Illness Post First Dose of Study Intervention | From 15 days post second dose up to DCO of 05 March 2021 or study discontinuation or unblinding or receipt of non-study COVID-19 vaccination, up to a maximum of 17 weeks | The incidence of SARS-CoV-2 RT-PCR-positive severe or critical symptomatic illness occurring post first dose of study intervention. The severity of COVID-19 was evaluated in participants with symptoms of COVID-19. Following are the findings regarding severe of critical symptomatic COVID-19: clinical signs at rest indicative of severe systemic illness; respiratory failure; evidence of shock; significant acute renal, hepatic, or neurologic dysfunction; admission to an intensive care unit; and death. |
| Number of Participants With COVID-19-Related Emergency Department Visits Post Second Dose of Study Intervention | From 15 days post second dose up to DCO of 05 March 2021 or study discontinuation or unblinding or receipt of non-study COVID-19 vaccination, up to a maximum of 17 weeks | The incidence of COVID-19-related emergency department visits occurring ≥ 15 days post second dose of study intervention (key secondary endpoint). |
| Geometric Mean Titers (GMTs) for SARS-CoV-2 Spike (S) and Receptor Binding Domain (RBD) Antibodies as Measured by Meso Scale Discovery (MSD) Serology Assay | Baseline (Day 1) and Days 15, 29, 43, 57, 90, 180, 360, and 730 | The GMT was calculated as the antilogarithm of Σ(log base 2 transformed titer/n), i.e. as the anti-logarithm transformation of the mean of the log-transformed titer, where 'n' is the number of participants with titer information. |
| Geometric Mean Fold Rise (GMFR) for SARS-CoV-2 S and RBD Antibodies as Measured by MSD Serology Assay | Days 15, 29, 43, 57, 90, 180, 360, and 730 | The fold rise was calculated as the ratio of the post-vaccination titer level to the pre-vaccination titer level. GMFR was calculated as anti-logarithm of Σ (log base 2 transformed (post-vaccination titer/ pre-vaccination titer)/n). Where 'n' is the number of participants with titer information. |
| Number of Participants With First Post-intervention Response for SARS-CoV-2 Nucleocapsid Antibodies Post Second Dose of Study Intervention | From 15 days post second dose up to DCO of 05 March 2021 or study discontinuation or unblinding or receipt of non-study COVID-19 vaccination, up to a maximum of 17 weeks | The incidence of the first post-intervention response (negative at baseline to positive post intervention with study intervention) for SARS-CoV-2 nucleocapsid antibodies occurring ≥ 15 days post second dose of study intervention (key secondary endpoint). |
| GMTs for SARS-CoV-2 Neutralizing Antibodies as Measured by Pseudo-neutralization Assay | Baseline (Day 1) and Days 15, 29, 43, 57, 90, 180, and 360 | The GMT was calculated as the antilogarithm of Σ(log base 2 transformed titer/n), i.e. as the anti-logarithm transformation of the mean of the log-transformed titer, where 'n' is the number of participants with titer information. |
| GMFR for SARS-CoV-2 Neutralizing Antibodies as Measured by Pseudo-neutralization Assay | Days 15, 29, 43, 57, 90, 180, and 360 | The fold rise was calculated as the ratio of the post-vaccination titer level to the pre-vaccination titer level. GMFR was calculated as anti-logarithm of Σ (log base 2 transformed (post-vaccination titer/ pre-vaccination titer)/n). Where 'n' is the number of participants with titer information. |
| Percentage of Participants With Seroresponse to SARS-CoV-2 Neutralizing Antibodies of AZD1222 as Measured by Pseudo-neutralization Assay | Days 15, 29, 43, 57, 90, 180, and 360 | The fold rise was calculated as the ratio of the post-vaccination titer level to the pre-vaccination titer level. The percentage of participants with a post-intervention seroresponse (≥ 4-fold rise in titers from baseline value to 28 days post each dose) to SARS-CoV-2 neutralizing antibodies of AZD1222 as measured by pseudo-neutralization assay is reported. |
| Number of Participants With COVID-19 Symptomatic Illness Post First Dose of Study Intervention | From Day 1 up to DCO of 05 March 2021 or study discontinuation or unblinding or receipt of non-study COVID-19 vaccination, up to a maximum of approximately 27 weeks | The incidence of SARS-CoV-2 RT-PCR-positive symptomatic illness occurring post first dose of study intervention. |
| Percentage of Participants With Seroresponse to the S and RBD Antigens of AZD1222 as Measured by MSD Serology Assay | Days 15, 29, 43, 57, 90, 180, 360, and 730 | The fold rise was calculated as the ratio of the post-vaccination titer level to the pre-vaccination titer level. The percentage of participants with a post-intervention seroresponse (≥ 4-fold rise in titers from baseline value to 28 days post each dose) to the S and RBD antigens of AZD1222 as measured by MSD serology assay is reported. |
| Number of Participants With First COVID-19 Symptomatic Illness Using Centers for Disease Control and Prevention (CDC) Criteria Post Second Dose of Study Intervention | From 15 days post second dose up to DCO of 05 March 2021 or study discontinuation or unblinding or receipt of non-study COVID-19 vaccination, up to a maximum of 17 weeks | The incidence of the first case of SARS-CoV-2 RT-PCR-positive symptomatic illness occurring ≥ 15 days post second dose of study intervention using CDC criteria. Participant must present with at least 1 of the following symptoms per CDC criteria: fever, shortness of breath, difficulty breathing, chills, cough, fatigue, muscle aches, body aches, headache, new loss of taste, new loss of smell, sore throat, congestion, runny nose, nausea, vomiting, or diarrhea. |
| Number of Participants With First COVID-19 Symptomatic Illness Using University of Oxford-Defined Symptom Criteria Post Second Dose of Study Intervention | From 15 days post second dose up to DCO of 05 March 2021 or study discontinuation or unblinding or receipt of non-study COVID-19 vaccination, up to a maximum of 17 weeks | The incidence of the first case of SARS-CoV-2 RT-PCR-positive symptomatic illness occurring ≥ 15 days post second dose of study intervention using University of Oxford-defined symptom criteria: new onset of fever (\> 100 °Fahrenheit \[\> 37.8 °Celsius\]), cough, shortness of breath, or anosmia/ageusia. |
| Number of Participants With First Symptomatic COVID-19 Regardless of Evidence of Prior SARS-CoV-2 Infection Post Second Dose of Study Intervention | From 15 days post second dose up to DCO of 05 March 2021 or study discontinuation or unblinding or receipt of non-study COVID-19 vaccination, up to a maximum of 17 weeks | The incidence of the first case of SARS-CoV-2 RT-PCR-positive symptomatic illness occurring ≥ 15 days post second dose of study intervention regardless of evidence of prior SARS-CoV-2 infection (key secondary endpoint). |
Countries
Chile, Peru, United States
Participant flow
Recruitment details
This Phase III randomized study was conducted in adult participants who were healthy or had medically stable chronic diseases and were at increased risk for severe acute respiratory syndrome-coronavirus-2 (SARS-CoV-2) acquisition and coronavirus disease-2019 (COVID-19) at 88 centers in Chile, Peru and United States of America between 28 August 2020 and 10 February 2023.
Pre-assignment details
The study had a screening period (14 days), followed by a treatment and follow-up period (up to 760 days). A total of 32450 participants were randomized in a 2:1 ratio to receive AZD1222 or placebo. One participant was enrolled at 2 sites and excluded from all analysis sets. The first participants randomized in each age group in the United States of America participated in a substudy to assess immunogenicity and reactogenicity.
Participants by arm
| Arm | Count |
|---|---|
| AZD1222 Participants were randomized to receive 2 IM doses of 5\*10\^10 vp (nominal, ± 1.5\*10\^10 vp) AZD1222 on Days 1 and 29. | 21,634 |
| Placebo Participants were randomized to receive 2 IM doses of placebo matching with AZD1222 on Days 1 and 29. | 10,816 |
| Total | 32,450 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Overall Study | Adverse Event | 0 | 1 |
| Overall Study | Death | 62 | 32 |
| Overall Study | Lost to Follow-up | 3,431 | 1,831 |
| Overall Study | Other | 35 | 16 |
| Overall Study | Physician Decision | 10 | 8 |
| Overall Study | Randomized but not Treated | 51 | 19 |
| Overall Study | Withdrawal by Subject | 1,946 | 1,696 |
Baseline characteristics
| Characteristic | Placebo | AZD1222 | Total |
|---|---|---|---|
| Age, Continuous | 50.2 years STANDARD_DEVIATION 15.86 | 50.2 years STANDARD_DEVIATION 15.92 | 50.2 years STANDARD_DEVIATION 15.9 |
| Race/Ethnicity, Customized American Indian or Alaska Native | 430 Participants | 855 Participants | 1285 Participants |
| Race/Ethnicity, Customized Asian | 483 Participants | 947 Participants | 1430 Participants |
| Race/Ethnicity, Customized Black or African American | 899 Participants | 1798 Participants | 2697 Participants |
| Race/Ethnicity, Customized Hispanic or Latino | 2456 Participants | 4787 Participants | 7243 Participants |
| Race/Ethnicity, Customized Multiple | 258 Participants | 513 Participants | 771 Participants |
| Race/Ethnicity, Customized Native Hawaiian or Other Pacific Islander | 21 Participants | 60 Participants | 81 Participants |
| Race/Ethnicity, Customized Not Hispanic or Latino | 8217 Participants | 16506 Participants | 24723 Participants |
| Race/Ethnicity, Customized Not reported | 127 Participants | 293 Participants | 398 Participants |
| Race/Ethnicity, Customized Unknown | 53 Participants | 101 Participants | 154 Participants |
| Race/Ethnicity, Customized White | 8534 Participants | 17100 Participants | 25634 Participants |
| Sex: Female, Male Female | 4797 Participants | 9603 Participants | 14400 Participants |
| Sex: Female, Male Male | 6019 Participants | 12031 Participants | 18050 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | 62 / 21,587 | 33 / 10,793 |
| other Total, other adverse events | 11,846 / 21,587 | 4,234 / 10,793 |
| serious Total, serious adverse events | 1,039 / 21,587 | 467 / 10,793 |
Outcome results
Primary
Number of Participants With Adverse Events (AEs) Post Each Dose of Study Intervention
An AE is the development of any untoward medical occurrence in a clinical study participant administered medicinal product and which does not necessarily have a causal relationship with this medicinal product. An AE can therefore be any unfavorable and unintended sign, symptom, or disease temporally associated with the use of a medicinal product, whether or not considered related to the medicinal product.
Time frame: From Day 1 up to 28 days post second dose of study intervention, approximately 57 days
Population: The safety analysis set included all participants who received at least 1 dose of study intervention from primary analysis data cut which is 1 participant less in placebo group than that from the final data cut.
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| AZD1222 | Number of Participants With Adverse Events (AEs) Post Each Dose of Study Intervention | After first dose | 5736 Participants |
| AZD1222 | Number of Participants With Adverse Events (AEs) Post Each Dose of Study Intervention | After second dose | 5074 Participants |
| AZD1222 | Number of Participants With Adverse Events (AEs) Post Each Dose of Study Intervention | After any dose | 8771 Participants |
| Placebo | Number of Participants With Adverse Events (AEs) Post Each Dose of Study Intervention | After first dose | 1926 Participants |
| Placebo | Number of Participants With Adverse Events (AEs) Post Each Dose of Study Intervention | After second dose | 1797 Participants |
| Placebo | Number of Participants With Adverse Events (AEs) Post Each Dose of Study Intervention | After any dose | 3201 Participants |
Primary
Number of Participants With Binary Response
A binary response, whereby a participant with negative serostatus at baseline is defined as a COVID-19 case if their first case of SARS-CoV-2 RT-PCR-positive symptomatic illness occurs ≥ 15 days post second dose of study intervention. Otherwise, a participant is not defined as a COVID-19 case. The primary efficacy analysis was performed once approximately 150 events meeting the primary efficacy outcome measure definition had occurred across the AZD1222 and placebo groups.
Time frame: From 15 days post second dose up to data cut-off date (DCO) of 05 March 2021 or study discontinuation or unblinding or receipt of non-study COVID-19 vaccination, up to a maximum of 17 weeks
Population: The fully vaccinated analysis set (FVS) included all participants in the full analysis set (FAS) who were seronegative at baseline, received 2 doses of study intervention, and who remained on-study 15 days after their second dose without having had a prior SARS-CoV-2 RT-PCR-positive confirmed COVID-19 infection.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| AZD1222 | Number of Participants With Binary Response | 73 Participants |
| Placebo | Number of Participants With Binary Response | 130 Participants |
Comparison: The 95% confidence interval (CI) and p-value were estimated based on Poisson regression with robust variance (including study arm and stratification factor \[age group at informed consent\] as covariates, and log of the follow up time as an offset).p-value: <0.00195% CI: [65.34, 80.47]Poisson regression with robust variance
Primary
Number of Participants With Local and Systemic Solicited AEs in the Substudy Only
Solicited AEs are local or systemic predefined events for assessment of reactogenicity. Solicited AEs were collected in a e-Diary only for participants in the substudy.
Time frame: From Day 1 up to 7 days post each dose of study intervention, approximately 14 days
Population: The safety analysis set included all participants who received at least 1 dose of study intervention. Only participants included in the substudy were analyzed.
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| AZD1222 | Number of Participants With Local and Systemic Solicited AEs in the Substudy Only | Solicited local AEs: After second dose | 977 Participants |
| AZD1222 | Number of Participants With Local and Systemic Solicited AEs in the Substudy Only | Solicited systemic AEs: After first dose | 1191 Participants |
| AZD1222 | Number of Participants With Local and Systemic Solicited AEs in the Substudy Only | Solicited local AEs: After first dose | 1250 Participants |
| AZD1222 | Number of Participants With Local and Systemic Solicited AEs in the Substudy Only | Solicited systemic AEs: After second dose | 862 Participants |
| AZD1222 | Number of Participants With Local and Systemic Solicited AEs in the Substudy Only | Solicited local AEs: After any dose | 1440 Participants |
| AZD1222 | Number of Participants With Local and Systemic Solicited AEs in the Substudy Only | Solicited systemic AEs: After any dose | 1395 Participants |
| Placebo | Number of Participants With Local and Systemic Solicited AEs in the Substudy Only | Solicited local AEs: After any dose | 239 Participants |
| Placebo | Number of Participants With Local and Systemic Solicited AEs in the Substudy Only | Solicited local AEs: After first dose | 173 Participants |
| Placebo | Number of Participants With Local and Systemic Solicited AEs in the Substudy Only | Solicited local AEs: After second dose | 120 Participants |
| Placebo | Number of Participants With Local and Systemic Solicited AEs in the Substudy Only | Solicited systemic AEs: After any dose | 519 Participants |
| Placebo | Number of Participants With Local and Systemic Solicited AEs in the Substudy Only | Solicited systemic AEs: After first dose | 415 Participants |
| Placebo | Number of Participants With Local and Systemic Solicited AEs in the Substudy Only | Solicited systemic AEs: After second dose | 314 Participants |
Primary
Number of Participants With Serious Adverse Events (SAE), Medically Attended Adverse Events (MAAE), and Adverse Event of Special Interest (AESI) Prior to Non-study COVID-19 Vaccination
An SAE is an AE occurring during any study phase that fulfils 1 or more of the following criteria: death; immediately life-threatening; in-participant hospitalization or prolongation of existing hospitalization; persistent or significant disability or incapacity; congenital abnormality or birth defect; an important medical event. AESIs were events of scientific and medical interest specific to the further understanding of the study intervention safety profile and required close monitoring and rapid communication by the investigators to the sponsor. MAAEs are defined as AEs leading to medically-attended visits that were not routine visits for physical examination or vaccination, such as an emergency room visit, or an otherwise unscheduled visit to or from medical personnel (medical doctor) for any reason. Different follow-up time between AZD1222 and Placebo groups (20223 versus 3893 participant years).
Time frame: From Day 1 up to receipt of non-study COVID-19 vaccination or a maximum of Day 760 for participants without non-study COVID-19 vaccination.
Population: The safety analysis set included all participants who received at least 1 dose of study intervention.
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| AZD1222 | Number of Participants With Serious Adverse Events (SAE), Medically Attended Adverse Events (MAAE), and Adverse Event of Special Interest (AESI) Prior to Non-study COVID-19 Vaccination | SAEs | 621 Participants |
| AZD1222 | Number of Participants With Serious Adverse Events (SAE), Medically Attended Adverse Events (MAAE), and Adverse Event of Special Interest (AESI) Prior to Non-study COVID-19 Vaccination | MAAEs | 4750 Participants |
| AZD1222 | Number of Participants With Serious Adverse Events (SAE), Medically Attended Adverse Events (MAAE), and Adverse Event of Special Interest (AESI) Prior to Non-study COVID-19 Vaccination | AESIs | 2516 Participants |
| Placebo | Number of Participants With Serious Adverse Events (SAE), Medically Attended Adverse Events (MAAE), and Adverse Event of Special Interest (AESI) Prior to Non-study COVID-19 Vaccination | SAEs | 136 Participants |
| Placebo | Number of Participants With Serious Adverse Events (SAE), Medically Attended Adverse Events (MAAE), and Adverse Event of Special Interest (AESI) Prior to Non-study COVID-19 Vaccination | MAAEs | 1256 Participants |
| Placebo | Number of Participants With Serious Adverse Events (SAE), Medically Attended Adverse Events (MAAE), and Adverse Event of Special Interest (AESI) Prior to Non-study COVID-19 Vaccination | AESIs | 591 Participants |
Secondary
Geometric Mean Fold Rise (GMFR) for SARS-CoV-2 S and RBD Antibodies as Measured by MSD Serology Assay
The fold rise was calculated as the ratio of the post-vaccination titer level to the pre-vaccination titer level. GMFR was calculated as anti-logarithm of Σ (log base 2 transformed (post-vaccination titer/ pre-vaccination titer)/n). Where 'n' is the number of participants with titer information.
Time frame: Days 15, 29, 43, 57, 90, 180, 360, and 730
Population: The immunogenicity analysis population included all participants in the safety analysis set who had no protocol deviations judged to have the potential to interfere with the generation or interpretation of an immune response. Only participants included in the substudy were analyzed.
| Arm | Measure | Group | Value (GEOMETRIC_MEAN) |
|---|---|---|---|
| AZD1222 | Geometric Mean Fold Rise (GMFR) for SARS-CoV-2 S and RBD Antibodies as Measured by MSD Serology Assay | S Antibody Titer: Day 15 | 34.28 ratio |
| AZD1222 | Geometric Mean Fold Rise (GMFR) for SARS-CoV-2 S and RBD Antibodies as Measured by MSD Serology Assay | S Antibody Titer: Day 29 | 108.35 ratio |
| AZD1222 | Geometric Mean Fold Rise (GMFR) for SARS-CoV-2 S and RBD Antibodies as Measured by MSD Serology Assay | S Antibody Titer: Day 43 | 455.38 ratio |
| AZD1222 | Geometric Mean Fold Rise (GMFR) for SARS-CoV-2 S and RBD Antibodies as Measured by MSD Serology Assay | S Antibody Titer: Day 57 | 373.44 ratio |
| AZD1222 | Geometric Mean Fold Rise (GMFR) for SARS-CoV-2 S and RBD Antibodies as Measured by MSD Serology Assay | S Antibody Titer: Day 90 | 274.05 ratio |
| AZD1222 | Geometric Mean Fold Rise (GMFR) for SARS-CoV-2 S and RBD Antibodies as Measured by MSD Serology Assay | S Antibody Titer: Day 180 | 138.44 ratio |
| AZD1222 | Geometric Mean Fold Rise (GMFR) for SARS-CoV-2 S and RBD Antibodies as Measured by MSD Serology Assay | S Antibody Titer: Day 360 | 121.12 ratio |
| AZD1222 | Geometric Mean Fold Rise (GMFR) for SARS-CoV-2 S and RBD Antibodies as Measured by MSD Serology Assay | S Antibody Titer: Day 730 | 3506.74 ratio |
| AZD1222 | Geometric Mean Fold Rise (GMFR) for SARS-CoV-2 S and RBD Antibodies as Measured by MSD Serology Assay | RBD Antibody Titer: Day 15 | 7.24 ratio |
| AZD1222 | Geometric Mean Fold Rise (GMFR) for SARS-CoV-2 S and RBD Antibodies as Measured by MSD Serology Assay | RBD Antibody Titer: Day 29 | 39.01 ratio |
| AZD1222 | Geometric Mean Fold Rise (GMFR) for SARS-CoV-2 S and RBD Antibodies as Measured by MSD Serology Assay | RBD Antibody Titer: Day 43 | 219.94 ratio |
| AZD1222 | Geometric Mean Fold Rise (GMFR) for SARS-CoV-2 S and RBD Antibodies as Measured by MSD Serology Assay | RBD Antibody Titer: Day 57 | 178.61 ratio |
| AZD1222 | Geometric Mean Fold Rise (GMFR) for SARS-CoV-2 S and RBD Antibodies as Measured by MSD Serology Assay | RBD Antibody Titer: Day 90 | 130.46 ratio |
| AZD1222 | Geometric Mean Fold Rise (GMFR) for SARS-CoV-2 S and RBD Antibodies as Measured by MSD Serology Assay | RBD Antibody Titer: Day 180 | 61.69 ratio |
| AZD1222 | Geometric Mean Fold Rise (GMFR) for SARS-CoV-2 S and RBD Antibodies as Measured by MSD Serology Assay | RBD Antibody Titer: Day 360 | 53.91 ratio |
| AZD1222 | Geometric Mean Fold Rise (GMFR) for SARS-CoV-2 S and RBD Antibodies as Measured by MSD Serology Assay | RBD Antibody Titer: Day 730 | 2103.65 ratio |
| Placebo | Geometric Mean Fold Rise (GMFR) for SARS-CoV-2 S and RBD Antibodies as Measured by MSD Serology Assay | RBD Antibody Titer: Day 730 | 106.35 ratio |
| Placebo | Geometric Mean Fold Rise (GMFR) for SARS-CoV-2 S and RBD Antibodies as Measured by MSD Serology Assay | S Antibody Titer: Day 15 | 0.97 ratio |
| Placebo | Geometric Mean Fold Rise (GMFR) for SARS-CoV-2 S and RBD Antibodies as Measured by MSD Serology Assay | RBD Antibody Titer: Day 15 | 1.00 ratio |
| Placebo | Geometric Mean Fold Rise (GMFR) for SARS-CoV-2 S and RBD Antibodies as Measured by MSD Serology Assay | S Antibody Titer: Day 29 | 0.92 ratio |
| Placebo | Geometric Mean Fold Rise (GMFR) for SARS-CoV-2 S and RBD Antibodies as Measured by MSD Serology Assay | RBD Antibody Titer: Day 90 | 1.41 ratio |
| Placebo | Geometric Mean Fold Rise (GMFR) for SARS-CoV-2 S and RBD Antibodies as Measured by MSD Serology Assay | S Antibody Titer: Day 43 | 1.08 ratio |
| Placebo | Geometric Mean Fold Rise (GMFR) for SARS-CoV-2 S and RBD Antibodies as Measured by MSD Serology Assay | RBD Antibody Titer: Day 29 | 1.01 ratio |
| Placebo | Geometric Mean Fold Rise (GMFR) for SARS-CoV-2 S and RBD Antibodies as Measured by MSD Serology Assay | S Antibody Titer: Day 57 | 1.10 ratio |
| Placebo | Geometric Mean Fold Rise (GMFR) for SARS-CoV-2 S and RBD Antibodies as Measured by MSD Serology Assay | RBD Antibody Titer: Day 360 | 11.18 ratio |
| Placebo | Geometric Mean Fold Rise (GMFR) for SARS-CoV-2 S and RBD Antibodies as Measured by MSD Serology Assay | S Antibody Titer: Day 90 | 1.61 ratio |
| Placebo | Geometric Mean Fold Rise (GMFR) for SARS-CoV-2 S and RBD Antibodies as Measured by MSD Serology Assay | RBD Antibody Titer: Day 43 | 1.05 ratio |
| Placebo | Geometric Mean Fold Rise (GMFR) for SARS-CoV-2 S and RBD Antibodies as Measured by MSD Serology Assay | S Antibody Titer: Day 180 | 3.33 ratio |
| Placebo | Geometric Mean Fold Rise (GMFR) for SARS-CoV-2 S and RBD Antibodies as Measured by MSD Serology Assay | RBD Antibody Titer: Day 180 | 3.13 ratio |
| Placebo | Geometric Mean Fold Rise (GMFR) for SARS-CoV-2 S and RBD Antibodies as Measured by MSD Serology Assay | S Antibody Titer: Day 360 | 17.44 ratio |
| Placebo | Geometric Mean Fold Rise (GMFR) for SARS-CoV-2 S and RBD Antibodies as Measured by MSD Serology Assay | RBD Antibody Titer: Day 57 | 1.10 ratio |
| Placebo | Geometric Mean Fold Rise (GMFR) for SARS-CoV-2 S and RBD Antibodies as Measured by MSD Serology Assay | S Antibody Titer: Day 730 | 295.66 ratio |
Secondary
Geometric Mean Titers (GMTs) for SARS-CoV-2 Spike (S) and Receptor Binding Domain (RBD) Antibodies as Measured by Meso Scale Discovery (MSD) Serology Assay
The GMT was calculated as the antilogarithm of Σ(log base 2 transformed titer/n), i.e. as the anti-logarithm transformation of the mean of the log-transformed titer, where 'n' is the number of participants with titer information.
Time frame: Baseline (Day 1) and Days 15, 29, 43, 57, 90, 180, 360, and 730
Population: The immunogenicity analysis population included all participants in the safety analysis set who had no protocol deviations judged to have the potential to interfere with the generation or interpretation of an immune response. Only participants included in the substudy were analyzed.
| Arm | Measure | Group | Value (GEOMETRIC_MEAN) |
|---|---|---|---|
| AZD1222 | Geometric Mean Titers (GMTs) for SARS-CoV-2 Spike (S) and Receptor Binding Domain (RBD) Antibodies as Measured by Meso Scale Discovery (MSD) Serology Assay | S Antibody Titer: Baseline (Day 1) | 53.18 arbitrary units per milliliter (AU/mL) |
| AZD1222 | Geometric Mean Titers (GMTs) for SARS-CoV-2 Spike (S) and Receptor Binding Domain (RBD) Antibodies as Measured by Meso Scale Discovery (MSD) Serology Assay | S Antibody Titer: Day 15 | 1820.10 arbitrary units per milliliter (AU/mL) |
| AZD1222 | Geometric Mean Titers (GMTs) for SARS-CoV-2 Spike (S) and Receptor Binding Domain (RBD) Antibodies as Measured by Meso Scale Discovery (MSD) Serology Assay | S Antibody Titer: Day 29 | 5782.09 arbitrary units per milliliter (AU/mL) |
| AZD1222 | Geometric Mean Titers (GMTs) for SARS-CoV-2 Spike (S) and Receptor Binding Domain (RBD) Antibodies as Measured by Meso Scale Discovery (MSD) Serology Assay | S Antibody Titer: Day 43 | 24105.87 arbitrary units per milliliter (AU/mL) |
| AZD1222 | Geometric Mean Titers (GMTs) for SARS-CoV-2 Spike (S) and Receptor Binding Domain (RBD) Antibodies as Measured by Meso Scale Discovery (MSD) Serology Assay | S Antibody Titer: Day 57 | 19488.64 arbitrary units per milliliter (AU/mL) |
| AZD1222 | Geometric Mean Titers (GMTs) for SARS-CoV-2 Spike (S) and Receptor Binding Domain (RBD) Antibodies as Measured by Meso Scale Discovery (MSD) Serology Assay | S Antibody Titer: Day 90 | 14583.30 arbitrary units per milliliter (AU/mL) |
| AZD1222 | Geometric Mean Titers (GMTs) for SARS-CoV-2 Spike (S) and Receptor Binding Domain (RBD) Antibodies as Measured by Meso Scale Discovery (MSD) Serology Assay | S Antibody Titer: Day 180 | 7483.04 arbitrary units per milliliter (AU/mL) |
| AZD1222 | Geometric Mean Titers (GMTs) for SARS-CoV-2 Spike (S) and Receptor Binding Domain (RBD) Antibodies as Measured by Meso Scale Discovery (MSD) Serology Assay | S Antibody Titer: Day 360 | 6686.81 arbitrary units per milliliter (AU/mL) |
| AZD1222 | Geometric Mean Titers (GMTs) for SARS-CoV-2 Spike (S) and Receptor Binding Domain (RBD) Antibodies as Measured by Meso Scale Discovery (MSD) Serology Assay | S Antibody Titer: Day 730 | 186727.78 arbitrary units per milliliter (AU/mL) |
| AZD1222 | Geometric Mean Titers (GMTs) for SARS-CoV-2 Spike (S) and Receptor Binding Domain (RBD) Antibodies as Measured by Meso Scale Discovery (MSD) Serology Assay | RBD Antibody Titer: Baseline (Day 1) | 133.6 arbitrary units per milliliter (AU/mL) |
| AZD1222 | Geometric Mean Titers (GMTs) for SARS-CoV-2 Spike (S) and Receptor Binding Domain (RBD) Antibodies as Measured by Meso Scale Discovery (MSD) Serology Assay | RBD Antibody Titer: Day 15 | 965.0 arbitrary units per milliliter (AU/mL) |
| AZD1222 | Geometric Mean Titers (GMTs) for SARS-CoV-2 Spike (S) and Receptor Binding Domain (RBD) Antibodies as Measured by Meso Scale Discovery (MSD) Serology Assay | RBD Antibody Titer: Day 29 | 5176.6 arbitrary units per milliliter (AU/mL) |
| AZD1222 | Geometric Mean Titers (GMTs) for SARS-CoV-2 Spike (S) and Receptor Binding Domain (RBD) Antibodies as Measured by Meso Scale Discovery (MSD) Serology Assay | RBD Antibody Titer: Day 43 | 29351.9 arbitrary units per milliliter (AU/mL) |
| AZD1222 | Geometric Mean Titers (GMTs) for SARS-CoV-2 Spike (S) and Receptor Binding Domain (RBD) Antibodies as Measured by Meso Scale Discovery (MSD) Serology Assay | RBD Antibody Titer: Day 57 | 23840.6 arbitrary units per milliliter (AU/mL) |
| AZD1222 | Geometric Mean Titers (GMTs) for SARS-CoV-2 Spike (S) and Receptor Binding Domain (RBD) Antibodies as Measured by Meso Scale Discovery (MSD) Serology Assay | RBD Antibody Titer: Day 90 | 17499.9 arbitrary units per milliliter (AU/mL) |
| AZD1222 | Geometric Mean Titers (GMTs) for SARS-CoV-2 Spike (S) and Receptor Binding Domain (RBD) Antibodies as Measured by Meso Scale Discovery (MSD) Serology Assay | RBD Antibody Titer: Day 180 | 8333.1 arbitrary units per milliliter (AU/mL) |
| AZD1222 | Geometric Mean Titers (GMTs) for SARS-CoV-2 Spike (S) and Receptor Binding Domain (RBD) Antibodies as Measured by Meso Scale Discovery (MSD) Serology Assay | RBD Antibody Titer: Day 360 | 7499.2 arbitrary units per milliliter (AU/mL) |
| AZD1222 | Geometric Mean Titers (GMTs) for SARS-CoV-2 Spike (S) and Receptor Binding Domain (RBD) Antibodies as Measured by Meso Scale Discovery (MSD) Serology Assay | RBD Antibody Titer: Day 730 | 276381.8 arbitrary units per milliliter (AU/mL) |
| Placebo | Geometric Mean Titers (GMTs) for SARS-CoV-2 Spike (S) and Receptor Binding Domain (RBD) Antibodies as Measured by Meso Scale Discovery (MSD) Serology Assay | RBD Antibody Titer: Day 57 | 151.6 arbitrary units per milliliter (AU/mL) |
| Placebo | Geometric Mean Titers (GMTs) for SARS-CoV-2 Spike (S) and Receptor Binding Domain (RBD) Antibodies as Measured by Meso Scale Discovery (MSD) Serology Assay | S Antibody Titer: Baseline (Day 1) | 54.68 arbitrary units per milliliter (AU/mL) |
| Placebo | Geometric Mean Titers (GMTs) for SARS-CoV-2 Spike (S) and Receptor Binding Domain (RBD) Antibodies as Measured by Meso Scale Discovery (MSD) Serology Assay | RBD Antibody Titer: Baseline (Day 1) | 138.9 arbitrary units per milliliter (AU/mL) |
| Placebo | Geometric Mean Titers (GMTs) for SARS-CoV-2 Spike (S) and Receptor Binding Domain (RBD) Antibodies as Measured by Meso Scale Discovery (MSD) Serology Assay | S Antibody Titer: Day 15 | 53.47 arbitrary units per milliliter (AU/mL) |
| Placebo | Geometric Mean Titers (GMTs) for SARS-CoV-2 Spike (S) and Receptor Binding Domain (RBD) Antibodies as Measured by Meso Scale Discovery (MSD) Serology Assay | RBD Antibody Titer: Day 730 | 19319.4 arbitrary units per milliliter (AU/mL) |
| Placebo | Geometric Mean Titers (GMTs) for SARS-CoV-2 Spike (S) and Receptor Binding Domain (RBD) Antibodies as Measured by Meso Scale Discovery (MSD) Serology Assay | S Antibody Titer: Day 29 | 53.64 arbitrary units per milliliter (AU/mL) |
| Placebo | Geometric Mean Titers (GMTs) for SARS-CoV-2 Spike (S) and Receptor Binding Domain (RBD) Antibodies as Measured by Meso Scale Discovery (MSD) Serology Assay | RBD Antibody Titer: Day 15 | 138.6 arbitrary units per milliliter (AU/mL) |
| Placebo | Geometric Mean Titers (GMTs) for SARS-CoV-2 Spike (S) and Receptor Binding Domain (RBD) Antibodies as Measured by Meso Scale Discovery (MSD) Serology Assay | S Antibody Titer: Day 43 | 58.15 arbitrary units per milliliter (AU/mL) |
| Placebo | Geometric Mean Titers (GMTs) for SARS-CoV-2 Spike (S) and Receptor Binding Domain (RBD) Antibodies as Measured by Meso Scale Discovery (MSD) Serology Assay | RBD Antibody Titer: Day 90 | 192.6 arbitrary units per milliliter (AU/mL) |
| Placebo | Geometric Mean Titers (GMTs) for SARS-CoV-2 Spike (S) and Receptor Binding Domain (RBD) Antibodies as Measured by Meso Scale Discovery (MSD) Serology Assay | S Antibody Titer: Day 57 | 58.30 arbitrary units per milliliter (AU/mL) |
| Placebo | Geometric Mean Titers (GMTs) for SARS-CoV-2 Spike (S) and Receptor Binding Domain (RBD) Antibodies as Measured by Meso Scale Discovery (MSD) Serology Assay | RBD Antibody Titer: Day 29 | 143.0 arbitrary units per milliliter (AU/mL) |
| Placebo | Geometric Mean Titers (GMTs) for SARS-CoV-2 Spike (S) and Receptor Binding Domain (RBD) Antibodies as Measured by Meso Scale Discovery (MSD) Serology Assay | S Antibody Titer: Day 90 | 87.51 arbitrary units per milliliter (AU/mL) |
| Placebo | Geometric Mean Titers (GMTs) for SARS-CoV-2 Spike (S) and Receptor Binding Domain (RBD) Antibodies as Measured by Meso Scale Discovery (MSD) Serology Assay | RBD Antibody Titer: Day 360 | 1912.3 arbitrary units per milliliter (AU/mL) |
| Placebo | Geometric Mean Titers (GMTs) for SARS-CoV-2 Spike (S) and Receptor Binding Domain (RBD) Antibodies as Measured by Meso Scale Discovery (MSD) Serology Assay | S Antibody Titer: Day 180 | 266.47 arbitrary units per milliliter (AU/mL) |
| Placebo | Geometric Mean Titers (GMTs) for SARS-CoV-2 Spike (S) and Receptor Binding Domain (RBD) Antibodies as Measured by Meso Scale Discovery (MSD) Serology Assay | RBD Antibody Titer: Day 43 | 145.7 arbitrary units per milliliter (AU/mL) |
| Placebo | Geometric Mean Titers (GMTs) for SARS-CoV-2 Spike (S) and Receptor Binding Domain (RBD) Antibodies as Measured by Meso Scale Discovery (MSD) Serology Assay | S Antibody Titer: Day 360 | 1268.45 arbitrary units per milliliter (AU/mL) |
| Placebo | Geometric Mean Titers (GMTs) for SARS-CoV-2 Spike (S) and Receptor Binding Domain (RBD) Antibodies as Measured by Meso Scale Discovery (MSD) Serology Assay | RBD Antibody Titer: Day 180 | 481.6 arbitrary units per milliliter (AU/mL) |
| Placebo | Geometric Mean Titers (GMTs) for SARS-CoV-2 Spike (S) and Receptor Binding Domain (RBD) Antibodies as Measured by Meso Scale Discovery (MSD) Serology Assay | S Antibody Titer: Day 730 | 19093.94 arbitrary units per milliliter (AU/mL) |
Secondary
GMFR for SARS-CoV-2 Neutralizing Antibodies as Measured by Pseudo-neutralization Assay
The fold rise was calculated as the ratio of the post-vaccination titer level to the pre-vaccination titer level. GMFR was calculated as anti-logarithm of Σ (log base 2 transformed (post-vaccination titer/ pre-vaccination titer)/n). Where 'n' is the number of participants with titer information.
Time frame: Days 15, 29, 43, 57, 90, 180, and 360
Population: The immunogenicity analysis population included all participants in the safety analysis set who had no protocol deviations judged to have the potential to interfere with the generation or interpretation of an immune response. Only participants included in the substudy were analyzed.
| Arm | Measure | Group | Value (GEOMETRIC_MEAN) |
|---|---|---|---|
| AZD1222 | GMFR for SARS-CoV-2 Neutralizing Antibodies as Measured by Pseudo-neutralization Assay | Day 43 | 10.91 ratio |
| AZD1222 | GMFR for SARS-CoV-2 Neutralizing Antibodies as Measured by Pseudo-neutralization Assay | Day 90 | 9.95 ratio |
| AZD1222 | GMFR for SARS-CoV-2 Neutralizing Antibodies as Measured by Pseudo-neutralization Assay | Day 29 | 3.24 ratio |
| AZD1222 | GMFR for SARS-CoV-2 Neutralizing Antibodies as Measured by Pseudo-neutralization Assay | Day 180 | 5.37 ratio |
| AZD1222 | GMFR for SARS-CoV-2 Neutralizing Antibodies as Measured by Pseudo-neutralization Assay | Day 57 | 12.32 ratio |
| AZD1222 | GMFR for SARS-CoV-2 Neutralizing Antibodies as Measured by Pseudo-neutralization Assay | Day 360 | 12.64 ratio |
| AZD1222 | GMFR for SARS-CoV-2 Neutralizing Antibodies as Measured by Pseudo-neutralization Assay | Day 15 | 2.03 ratio |
| Placebo | GMFR for SARS-CoV-2 Neutralizing Antibodies as Measured by Pseudo-neutralization Assay | Day 360 | 2.31 ratio |
| Placebo | GMFR for SARS-CoV-2 Neutralizing Antibodies as Measured by Pseudo-neutralization Assay | Day 15 | 1.01 ratio |
| Placebo | GMFR for SARS-CoV-2 Neutralizing Antibodies as Measured by Pseudo-neutralization Assay | Day 29 | 1.07 ratio |
| Placebo | GMFR for SARS-CoV-2 Neutralizing Antibodies as Measured by Pseudo-neutralization Assay | Day 43 | 1.05 ratio |
| Placebo | GMFR for SARS-CoV-2 Neutralizing Antibodies as Measured by Pseudo-neutralization Assay | Day 57 | 1.08 ratio |
| Placebo | GMFR for SARS-CoV-2 Neutralizing Antibodies as Measured by Pseudo-neutralization Assay | Day 90 | 1.94 ratio |
| Placebo | GMFR for SARS-CoV-2 Neutralizing Antibodies as Measured by Pseudo-neutralization Assay | Day 180 | 2.22 ratio |
Secondary
GMTs for SARS-CoV-2 Neutralizing Antibodies as Measured by Pseudo-neutralization Assay
The GMT was calculated as the antilogarithm of Σ(log base 2 transformed titer/n), i.e. as the anti-logarithm transformation of the mean of the log-transformed titer, where 'n' is the number of participants with titer information.
Time frame: Baseline (Day 1) and Days 15, 29, 43, 57, 90, 180, and 360
Population: The immunogenicity analysis population included all participants in the safety analysis set who had no protocol deviations judged to have the potential to interfere with the generation or interpretation of an immune response. Only participants included in the substudy were analyzed.
| Arm | Measure | Group | Value (GEOMETRIC_MEAN) |
|---|---|---|---|
| AZD1222 | GMTs for SARS-CoV-2 Neutralizing Antibodies as Measured by Pseudo-neutralization Assay | Baseline (Day 1) | 20.6 AU/mL |
| AZD1222 | GMTs for SARS-CoV-2 Neutralizing Antibodies as Measured by Pseudo-neutralization Assay | Day 15 | 41.7 AU/mL |
| AZD1222 | GMTs for SARS-CoV-2 Neutralizing Antibodies as Measured by Pseudo-neutralization Assay | Day 29 | 65.9 AU/mL |
| AZD1222 | GMTs for SARS-CoV-2 Neutralizing Antibodies as Measured by Pseudo-neutralization Assay | Day 43 | 221.3 AU/mL |
| AZD1222 | GMTs for SARS-CoV-2 Neutralizing Antibodies as Measured by Pseudo-neutralization Assay | Day 57 | 251.8 AU/mL |
| AZD1222 | GMTs for SARS-CoV-2 Neutralizing Antibodies as Measured by Pseudo-neutralization Assay | Day 90 | 206.1 AU/mL |
| AZD1222 | GMTs for SARS-CoV-2 Neutralizing Antibodies as Measured by Pseudo-neutralization Assay | Day 180 | 112.9 AU/mL |
| AZD1222 | GMTs for SARS-CoV-2 Neutralizing Antibodies as Measured by Pseudo-neutralization Assay | Day 360 | 265.7 AU/mL |
| Placebo | GMTs for SARS-CoV-2 Neutralizing Antibodies as Measured by Pseudo-neutralization Assay | Day 360 | 46.3 AU/mL |
| Placebo | GMTs for SARS-CoV-2 Neutralizing Antibodies as Measured by Pseudo-neutralization Assay | Baseline (Day 1) | 21.4 AU/mL |
| Placebo | GMTs for SARS-CoV-2 Neutralizing Antibodies as Measured by Pseudo-neutralization Assay | Day 57 | 23.3 AU/mL |
| Placebo | GMTs for SARS-CoV-2 Neutralizing Antibodies as Measured by Pseudo-neutralization Assay | Day 15 | 21.7 AU/mL |
| Placebo | GMTs for SARS-CoV-2 Neutralizing Antibodies as Measured by Pseudo-neutralization Assay | Day 180 | 51.3 AU/mL |
| Placebo | GMTs for SARS-CoV-2 Neutralizing Antibodies as Measured by Pseudo-neutralization Assay | Day 29 | 23.0 AU/mL |
| Placebo | GMTs for SARS-CoV-2 Neutralizing Antibodies as Measured by Pseudo-neutralization Assay | Day 90 | 37.5 AU/mL |
| Placebo | GMTs for SARS-CoV-2 Neutralizing Antibodies as Measured by Pseudo-neutralization Assay | Day 43 | 22.6 AU/mL |
Secondary
Number of Participants With COVID-19-Related Emergency Department Visits Post Second Dose of Study Intervention
The incidence of COVID-19-related emergency department visits occurring ≥ 15 days post second dose of study intervention (key secondary endpoint).
Time frame: From 15 days post second dose up to DCO of 05 March 2021 or study discontinuation or unblinding or receipt of non-study COVID-19 vaccination, up to a maximum of 17 weeks
Population: The FVS included all participants in the FAS who were seronegative at baseline, received 2 doses of study intervention, and who remained on-study 15 days after their second dose without having had a prior SARS-CoV-2 RT-PCR-positive confirmed COVID-19 infection.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| AZD1222 | Number of Participants With COVID-19-Related Emergency Department Visits Post Second Dose of Study Intervention | 1 Participants |
| Placebo | Number of Participants With COVID-19-Related Emergency Department Visits Post Second Dose of Study Intervention | 9 Participants |
Comparison: The 95% CI and p-value were estimated based on Poisson regression with robust variance (including study arm and stratification factor \[age group at informed consent\] as covariates, and log of the follow up time as an offset).p-value: 0.00595% CI: [58.98, 99.34]Poisson regression with robust variance
Secondary
Number of Participants With COVID-19 Severe or Critical Symptomatic Illness Post First Dose of Study Intervention
The incidence of SARS-CoV-2 RT-PCR-positive severe or critical symptomatic illness occurring post first dose of study intervention. The severity of COVID-19 was evaluated in participants with symptoms of COVID-19. Following are the findings regarding severe of critical symptomatic COVID-19: clinical signs at rest indicative of severe systemic illness; respiratory failure; evidence of shock; significant acute renal, hepatic, or neurologic dysfunction; admission to an intensive care unit; and death.
Time frame: From 15 days post second dose up to DCO of 05 March 2021 or study discontinuation or unblinding or receipt of non-study COVID-19 vaccination, up to a maximum of 17 weeks
Population: The FAS included all randomized participants who received at least 1 dose of study intervention, irrespective of their protocol adherence and continued participation in the study. Only participants who are seronegative at baseline were analyzed.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| AZD1222 | Number of Participants With COVID-19 Severe or Critical Symptomatic Illness Post First Dose of Study Intervention | 5 Participants |
| Placebo | Number of Participants With COVID-19 Severe or Critical Symptomatic Illness Post First Dose of Study Intervention | 16 Participants |
Comparison: The 95% CI were estimated based on Poisson regression with robust variance (including study arm and age group at screening (18-65 years, ≥ 65 years) as covariates and log of the follow-up time as an offset).p-value: <0.00195% CI: [58.97, 94.5]Poisson regression with robust variance
Secondary
Number of Participants With COVID-19 Severe or Critical Symptomatic Illness Post Second Dose of Study Intervention
The incidence of SARS-CoV-2 RT-PCR-positive severe or critical symptomatic illness occurring ≥ 15 days post second dose of study intervention. The severity of COVID-19 was evaluated in participants with symptoms of COVID-19. Following are the findings regarding severe of critical symptomatic COVID-19: clinical signs at rest indicative of severe systemic illness; respiratory failure; evidence of shock; significant acute renal, hepatic, or neurologic dysfunction; admission to an intensive care unit; and death (key secondary endpoint).
Time frame: From 15 days post second dose up to DCO of 05 March 2021 or study discontinuation or unblinding or receipt of non-study COVID-19 vaccination, up to a maximum of 17 weeks
Population: The FVS included all participants in the FAS who were seronegative at baseline, received 2 doses of study intervention, and who remained on-study 15 days after their second dose without having had a prior SARS-CoV-2 RT-PCR-positive confirmed COVID-19 infection.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| AZD1222 | Number of Participants With COVID-19 Severe or Critical Symptomatic Illness Post Second Dose of Study Intervention | 0 Participants |
| Placebo | Number of Participants With COVID-19 Severe or Critical Symptomatic Illness Post Second Dose of Study Intervention | 8 Participants |
Comparison: The exact 1-sided 97.5% CI and p-value were estimated based on stratified Poisson regression with exact conditional method (including study arm and stratification factor \[age group at informed consent\] as strata factor and log of total number of participants for each combination of study arm and strata as an offset).p-value: <0.001Poisson regression exact conditional
Secondary
Number of Participants With COVID-19 Symptomatic Illness Post First Dose of Study Intervention
The incidence of SARS-CoV-2 RT-PCR-positive symptomatic illness occurring post first dose of study intervention.
Time frame: From Day 1 up to DCO of 05 March 2021 or study discontinuation or unblinding or receipt of non-study COVID-19 vaccination, up to a maximum of approximately 27 weeks
Population: The FAS included all randomized participants who received at least 1 dose of study intervention, irrespective of their protocol adherence and continued participation in the study. Only participants who are seronegative at baseline were analyzed.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| AZD1222 | Number of Participants With COVID-19 Symptomatic Illness Post First Dose of Study Intervention | 287 Participants |
| Placebo | Number of Participants With COVID-19 Symptomatic Illness Post First Dose of Study Intervention | 303 Participants |
Comparison: The 95% CI were estimated based on Poisson regression with robust variance (including study arm and age group at screening (18-65 years, ≥ 65 years) as covariates and log of the follow-up time as an offset).95% CI: [46.48, 61.26]
Secondary
Number of Participants With First COVID-19 Symptomatic Illness Using Centers for Disease Control and Prevention (CDC) Criteria Post Second Dose of Study Intervention
The incidence of the first case of SARS-CoV-2 RT-PCR-positive symptomatic illness occurring ≥ 15 days post second dose of study intervention using CDC criteria. Participant must present with at least 1 of the following symptoms per CDC criteria: fever, shortness of breath, difficulty breathing, chills, cough, fatigue, muscle aches, body aches, headache, new loss of taste, new loss of smell, sore throat, congestion, runny nose, nausea, vomiting, or diarrhea.
Time frame: From 15 days post second dose up to DCO of 05 March 2021 or study discontinuation or unblinding or receipt of non-study COVID-19 vaccination, up to a maximum of 17 weeks
Population: The FVS included all participants in the FAS who were seronegative at baseline, received 2 doses of study intervention, and who remained on-study 15 days after their second dose without having had a prior SARS-CoV-2 RT-PCR-positive confirmed COVID-19 infection.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| AZD1222 | Number of Participants With First COVID-19 Symptomatic Illness Using Centers for Disease Control and Prevention (CDC) Criteria Post Second Dose of Study Intervention | 95 Participants |
| Placebo | Number of Participants With First COVID-19 Symptomatic Illness Using Centers for Disease Control and Prevention (CDC) Criteria Post Second Dose of Study Intervention | 145 Participants |
Comparison: The 95% CI and p-value were estimated based on Poisson regression with robust variance (including study arm and stratification factor \[age group at informed consent\] as covariates, and log of the follow up time as an offset).p-value: <0.00195% CI: [60.68, 76.57]Poisson regression with robust variance
Secondary
Number of Participants With First COVID-19 Symptomatic Illness Using University of Oxford-Defined Symptom Criteria Post Second Dose of Study Intervention
The incidence of the first case of SARS-CoV-2 RT-PCR-positive symptomatic illness occurring ≥ 15 days post second dose of study intervention using University of Oxford-defined symptom criteria: new onset of fever (\> 100 °Fahrenheit \[\> 37.8 °Celsius\]), cough, shortness of breath, or anosmia/ageusia.
Time frame: From 15 days post second dose up to DCO of 05 March 2021 or study discontinuation or unblinding or receipt of non-study COVID-19 vaccination, up to a maximum of 17 weeks
Population: The FVS included all participants in the FAS who were seronegative at baseline, received 2 doses of study intervention, and who remained on-study 15 days after their second dose without having had a prior SARS-CoV-2 RT-PCR-positive confirmed COVID-19 infection.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| AZD1222 | Number of Participants With First COVID-19 Symptomatic Illness Using University of Oxford-Defined Symptom Criteria Post Second Dose of Study Intervention | 86 Participants |
| Placebo | Number of Participants With First COVID-19 Symptomatic Illness Using University of Oxford-Defined Symptom Criteria Post Second Dose of Study Intervention | 136 Participants |
Comparison: The 95% CI and p-value were estimated based on Poisson regression with robust variance (including study arm and stratification factor \[age group at informed consent\] as covariates, and log of the follow up time as an offset).p-value: <0.00195% CI: [61.62, 77.64]Poisson regression with robust variance
Secondary
Number of Participants With First Post-intervention Response for SARS-CoV-2 Nucleocapsid Antibodies Post Second Dose of Study Intervention
The incidence of the first post-intervention response (negative at baseline to positive post intervention with study intervention) for SARS-CoV-2 nucleocapsid antibodies occurring ≥ 15 days post second dose of study intervention (key secondary endpoint).
Time frame: From 15 days post second dose up to DCO of 05 March 2021 or study discontinuation or unblinding or receipt of non-study COVID-19 vaccination, up to a maximum of 17 weeks
Population: The FVS included all participants in the FAS who were seronegative at baseline, received 2 doses of study intervention, and who remained on-study 15 days after their second dose without having had a prior SARS-CoV-2 RT-PCR-positive confirmed COVID-19 infection.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| AZD1222 | Number of Participants With First Post-intervention Response for SARS-CoV-2 Nucleocapsid Antibodies Post Second Dose of Study Intervention | 156 Participants |
| Placebo | Number of Participants With First Post-intervention Response for SARS-CoV-2 Nucleocapsid Antibodies Post Second Dose of Study Intervention | 202 Participants |
Comparison: The 95% CI and p-value were estimated based on Poisson regression with robust variance (including study arm and stratification factor \[age group at informed consent\] as covariates, and log of the follow up time as an offset).p-value: <0.00195% CI: [56.05, 71.03]Poisson regression with robust variance
Secondary
Number of Participants With First Symptomatic COVID-19 Regardless of Evidence of Prior SARS-CoV-2 Infection Post Second Dose of Study Intervention
The incidence of the first case of SARS-CoV-2 RT-PCR-positive symptomatic illness occurring ≥ 15 days post second dose of study intervention regardless of evidence of prior SARS-CoV-2 infection (key secondary endpoint).
Time frame: From 15 days post second dose up to DCO of 05 March 2021 or study discontinuation or unblinding or receipt of non-study COVID-19 vaccination, up to a maximum of 17 weeks
Population: The FVS regardless of prior SARS-COV-2 infection included all participants in the FAS who were seronegative at baseline, received 2 doses of study intervention, and who remained on-study 15 days after their second dose.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| AZD1222 | Number of Participants With First Symptomatic COVID-19 Regardless of Evidence of Prior SARS-CoV-2 Infection Post Second Dose of Study Intervention | 76 Participants |
| Placebo | Number of Participants With First Symptomatic COVID-19 Regardless of Evidence of Prior SARS-CoV-2 Infection Post Second Dose of Study Intervention | 135 Participants |
Comparison: The 95% CI and p-value were estimated based on Poisson regression with robust variance (including study arm and stratification factor \[age group at informed consent\] as covariates, and log of the follow up time as an offset).p-value: <0.00195% CI: [65.13, 80.13]Poisson regression with robust variance
Secondary
Percentage of Participants With Seroresponse to SARS-CoV-2 Neutralizing Antibodies of AZD1222 as Measured by Pseudo-neutralization Assay
The fold rise was calculated as the ratio of the post-vaccination titer level to the pre-vaccination titer level. The percentage of participants with a post-intervention seroresponse (≥ 4-fold rise in titers from baseline value to 28 days post each dose) to SARS-CoV-2 neutralizing antibodies of AZD1222 as measured by pseudo-neutralization assay is reported.
Time frame: Days 15, 29, 43, 57, 90, 180, and 360
Population: The immunogenicity analysis population included all participants in the safety analysis set who had no protocol deviations judged to have the potential to interfere with the generation or interpretation of an immune response. Only participants included in the substudy were analyzed.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| AZD1222 | Percentage of Participants With Seroresponse to SARS-CoV-2 Neutralizing Antibodies of AZD1222 as Measured by Pseudo-neutralization Assay | Day 43 | 84.4 percentage of participants |
| AZD1222 | Percentage of Participants With Seroresponse to SARS-CoV-2 Neutralizing Antibodies of AZD1222 as Measured by Pseudo-neutralization Assay | Day 90 | 83.3 percentage of participants |
| AZD1222 | Percentage of Participants With Seroresponse to SARS-CoV-2 Neutralizing Antibodies of AZD1222 as Measured by Pseudo-neutralization Assay | Day 29 | 41.1 percentage of participants |
| AZD1222 | Percentage of Participants With Seroresponse to SARS-CoV-2 Neutralizing Antibodies of AZD1222 as Measured by Pseudo-neutralization Assay | Day 180 | 51.5 percentage of participants |
| AZD1222 | Percentage of Participants With Seroresponse to SARS-CoV-2 Neutralizing Antibodies of AZD1222 as Measured by Pseudo-neutralization Assay | Day 57 | 84.4 percentage of participants |
| AZD1222 | Percentage of Participants With Seroresponse to SARS-CoV-2 Neutralizing Antibodies of AZD1222 as Measured by Pseudo-neutralization Assay | Day 360 | 53.8 percentage of participants |
| AZD1222 | Percentage of Participants With Seroresponse to SARS-CoV-2 Neutralizing Antibodies of AZD1222 as Measured by Pseudo-neutralization Assay | Day 15 | 24.8 percentage of participants |
| Placebo | Percentage of Participants With Seroresponse to SARS-CoV-2 Neutralizing Antibodies of AZD1222 as Measured by Pseudo-neutralization Assay | Day 360 | 28.6 percentage of participants |
| Placebo | Percentage of Participants With Seroresponse to SARS-CoV-2 Neutralizing Antibodies of AZD1222 as Measured by Pseudo-neutralization Assay | Day 15 | 0.3 percentage of participants |
| Placebo | Percentage of Participants With Seroresponse to SARS-CoV-2 Neutralizing Antibodies of AZD1222 as Measured by Pseudo-neutralization Assay | Day 29 | 1.8 percentage of participants |
| Placebo | Percentage of Participants With Seroresponse to SARS-CoV-2 Neutralizing Antibodies of AZD1222 as Measured by Pseudo-neutralization Assay | Day 43 | 1.9 percentage of participants |
| Placebo | Percentage of Participants With Seroresponse to SARS-CoV-2 Neutralizing Antibodies of AZD1222 as Measured by Pseudo-neutralization Assay | Day 57 | 2.2 percentage of participants |
| Placebo | Percentage of Participants With Seroresponse to SARS-CoV-2 Neutralizing Antibodies of AZD1222 as Measured by Pseudo-neutralization Assay | Day 90 | 10.0 percentage of participants |
| Placebo | Percentage of Participants With Seroresponse to SARS-CoV-2 Neutralizing Antibodies of AZD1222 as Measured by Pseudo-neutralization Assay | Day 180 | 22.0 percentage of participants |
Secondary
Percentage of Participants With Seroresponse to the S and RBD Antigens of AZD1222 as Measured by MSD Serology Assay
The fold rise was calculated as the ratio of the post-vaccination titer level to the pre-vaccination titer level. The percentage of participants with a post-intervention seroresponse (≥ 4-fold rise in titers from baseline value to 28 days post each dose) to the S and RBD antigens of AZD1222 as measured by MSD serology assay is reported.
Time frame: Days 15, 29, 43, 57, 90, 180, 360, and 730
Population: The immunogenicity analysis population included all participants in the safety analysis set who had no protocol deviations judged to have the potential to interfere with the generation or interpretation of an immune response. Only participants included in the substudy were analyzed.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| AZD1222 | Percentage of Participants With Seroresponse to the S and RBD Antigens of AZD1222 as Measured by MSD Serology Assay | S Antibody Titer: Day 15 | 89.8 percentage of participants |
| AZD1222 | Percentage of Participants With Seroresponse to the S and RBD Antigens of AZD1222 as Measured by MSD Serology Assay | S Antibody Titer: Day 29 | 97.1 percentage of participants |
| AZD1222 | Percentage of Participants With Seroresponse to the S and RBD Antigens of AZD1222 as Measured by MSD Serology Assay | S Antibody Titer: Day 43 | 99.4 percentage of participants |
| AZD1222 | Percentage of Participants With Seroresponse to the S and RBD Antigens of AZD1222 as Measured by MSD Serology Assay | S Antibody Titer: Day 57 | 99.3 percentage of participants |
| AZD1222 | Percentage of Participants With Seroresponse to the S and RBD Antigens of AZD1222 as Measured by MSD Serology Assay | S Antibody Titer: Day 90 | 99.3 percentage of participants |
| AZD1222 | Percentage of Participants With Seroresponse to the S and RBD Antigens of AZD1222 as Measured by MSD Serology Assay | S Antibody Titer: Day 180 | 98.3 percentage of participants |
| AZD1222 | Percentage of Participants With Seroresponse to the S and RBD Antigens of AZD1222 as Measured by MSD Serology Assay | S Antibody Titer: Day 360 | 96.1 percentage of participants |
| AZD1222 | Percentage of Participants With Seroresponse to the S and RBD Antigens of AZD1222 as Measured by MSD Serology Assay | S Antibody Titer: Day 730 | 100.0 percentage of participants |
| AZD1222 | Percentage of Participants With Seroresponse to the S and RBD Antigens of AZD1222 as Measured by MSD Serology Assay | RBD Antibody Titer: Day 15 | 61.3 percentage of participants |
| AZD1222 | Percentage of Participants With Seroresponse to the S and RBD Antigens of AZD1222 as Measured by MSD Serology Assay | RBD Antibody Titer: Day 29 | 92.2 percentage of participants |
| AZD1222 | Percentage of Participants With Seroresponse to the S and RBD Antigens of AZD1222 as Measured by MSD Serology Assay | RBD Antibody Titer: Day 43 | 98.8 percentage of participants |
| AZD1222 | Percentage of Participants With Seroresponse to the S and RBD Antigens of AZD1222 as Measured by MSD Serology Assay | RBD Antibody Titer: Day 57 | 98.7 percentage of participants |
| AZD1222 | Percentage of Participants With Seroresponse to the S and RBD Antigens of AZD1222 as Measured by MSD Serology Assay | RBD Antibody Titer: Day 90 | 98.6 percentage of participants |
| AZD1222 | Percentage of Participants With Seroresponse to the S and RBD Antigens of AZD1222 as Measured by MSD Serology Assay | RBD Antibody Titer: Day 180 | 96.3 percentage of participants |
| AZD1222 | Percentage of Participants With Seroresponse to the S and RBD Antigens of AZD1222 as Measured by MSD Serology Assay | RBD Antibody Titer: Day 360 | 89.8 percentage of participants |
| AZD1222 | Percentage of Participants With Seroresponse to the S and RBD Antigens of AZD1222 as Measured by MSD Serology Assay | RBD Antibody Titer: Day 730 | 99.3 percentage of participants |
| Placebo | Percentage of Participants With Seroresponse to the S and RBD Antigens of AZD1222 as Measured by MSD Serology Assay | RBD Antibody Titer: Day 730 | 86.4 percentage of participants |
| Placebo | Percentage of Participants With Seroresponse to the S and RBD Antigens of AZD1222 as Measured by MSD Serology Assay | S Antibody Titer: Day 15 | 1.1 percentage of participants |
| Placebo | Percentage of Participants With Seroresponse to the S and RBD Antigens of AZD1222 as Measured by MSD Serology Assay | RBD Antibody Titer: Day 15 | 0.4 percentage of participants |
| Placebo | Percentage of Participants With Seroresponse to the S and RBD Antigens of AZD1222 as Measured by MSD Serology Assay | S Antibody Titer: Day 29 | 1.6 percentage of participants |
| Placebo | Percentage of Participants With Seroresponse to the S and RBD Antigens of AZD1222 as Measured by MSD Serology Assay | RBD Antibody Titer: Day 90 | 7.7 percentage of participants |
| Placebo | Percentage of Participants With Seroresponse to the S and RBD Antigens of AZD1222 as Measured by MSD Serology Assay | S Antibody Titer: Day 43 | 2.5 percentage of participants |
| Placebo | Percentage of Participants With Seroresponse to the S and RBD Antigens of AZD1222 as Measured by MSD Serology Assay | RBD Antibody Titer: Day 29 | 1.0 percentage of participants |
| Placebo | Percentage of Participants With Seroresponse to the S and RBD Antigens of AZD1222 as Measured by MSD Serology Assay | S Antibody Titer: Day 57 | 3.2 percentage of participants |
| Placebo | Percentage of Participants With Seroresponse to the S and RBD Antigens of AZD1222 as Measured by MSD Serology Assay | RBD Antibody Titer: Day 360 | 50.0 percentage of participants |
| Placebo | Percentage of Participants With Seroresponse to the S and RBD Antigens of AZD1222 as Measured by MSD Serology Assay | S Antibody Titer: Day 90 | 8.9 percentage of participants |
| Placebo | Percentage of Participants With Seroresponse to the S and RBD Antigens of AZD1222 as Measured by MSD Serology Assay | RBD Antibody Titer: Day 43 | 2.0 percentage of participants |
| Placebo | Percentage of Participants With Seroresponse to the S and RBD Antigens of AZD1222 as Measured by MSD Serology Assay | S Antibody Titer: Day 180 | 23.3 percentage of participants |
| Placebo | Percentage of Participants With Seroresponse to the S and RBD Antigens of AZD1222 as Measured by MSD Serology Assay | RBD Antibody Titer: Day 180 | 22.6 percentage of participants |
| Placebo | Percentage of Participants With Seroresponse to the S and RBD Antigens of AZD1222 as Measured by MSD Serology Assay | S Antibody Titer: Day 360 | 54.3 percentage of participants |
| Placebo | Percentage of Participants With Seroresponse to the S and RBD Antigens of AZD1222 as Measured by MSD Serology Assay | RBD Antibody Titer: Day 57 | 2.6 percentage of participants |
| Placebo | Percentage of Participants With Seroresponse to the S and RBD Antigens of AZD1222 as Measured by MSD Serology Assay | S Antibody Titer: Day 730 | 90.9 percentage of participants |